Can elevated lactate and LDH produce a false positive enzymatic ethanol result in live patients presenting to the emergency department?

BACKGROUND: There have been allegations in the courtroom that elevated serum lactic acid in trauma victims can yield a falsely elevated serum ethanol assay. Most hospitals utilize an indirect method of ethanol measurement where a serum sample is added to a mix of alcohol dehydrogenase and oxidized nicotinamide adenine dinucleotide (NAD+). This allows any ethanol in the patient's serum to be metabolized to acetaldehyde, and in the process results in the reduction of NAD + to NADH. NADH is then measured using spectrophotometry. The courtroom allegation stems from the concept that oxidation of lactate to pyruvate by lactate dehydrogenase (LDH) results in the same molar-for-molar reduction of NAD + to NADH, and could therefore theoretically cause patients with elevated lactate and LDH to have a falsely elevated ethanol concentration. METHODS: Patients with elevated lactic acid and LDH concentrations who presented to a university hospital from 20 April 2015 to 13 December 2015 were identified to provide possible test specimens. If a sufficient amount of serum was available, the sample was used to re-run the lactate and LDH concentration simultaneously with an enzymatic ethanol assay. Any samples that had elevated lactic acid and LDH concentrations on this retesting, and also yielded a positive ethanol concentration, were sent for confirmatory gas chromatography testing of ethanol concentrations. A control group of 20 samples with normal lactate and LDH were included. RESULTS: A total of 37 samples were included in the final analysis. Only 4 patients had an elevated enzymatic ethanol concentration, and all 4 also had a measurable GC ethanol concentration. The lactate in this dataset ranged from 2.4 to 24.2 mmol/L, with a mean of 6.53 mmol/L (normal value 0.5-2.2). The LDH ranged from 242 to 8838 U/L with a mean of 1695 U/L (normal value 122-225 U/L). Twenty control samples were run on patients with normal lactate and LDH, none of which yielded a positive enzymatic ethanol result. CONCLUSIONS: This data does not support the contention that an elevated LDH and lactate can yield a false positive serum ethanol result as run by enzymatic ethanol assay in live patients presenting to the emergency department.

A systematic review of the evidence for acute tolerance to alcohol - the "Mellanby effect".

OBJECTIVE: To review the evidence for "the Mellanby effect", that is, whether the response to a given blood alcohol concentration (BAC) is more marked when BAC is rising than at the same concentration when BAC is falling. METHODS: We systematically searched the databases EMBASE, Medline, and Scopus up to and including December 2016 using text words "tolerance", "ascending", "descending" or "Mellanby" with Medline term "exp *alcohol/" or "exp *drinking behavior/" or equivalent. Articles were identified for further examination by title or abstract; full text articles were retained for analysis if they dealt with acute (within dose) alcohol tolerance in human subjects and provided quantitative data on both the ascending and descending parts of the BAC-time curve. Reference lists of identified works were scanned for other potentially relevant material. We extracted and analyzed data on the subjective and objective assessment of alcohol effects. RESULTS: We identified and screened 386 unique articles, of which 127 full-text articles were assessed; one provided no qualitative results, 62 involved no human study, 25 did not consider acute tolerance within dose, and 13 failed to provide data on both ascending and descending BAC. We extracted data from the 26 remaining articles. The studies were highly heterogeneous. Most were small, examining a total of 770 subjects, of whom 564 received alcohol and were analyzed in groups of median size 10 (range 5-38), sometimes subdivided on the basis of drinking or family history. Subjects were often young white men. Doses of alcohol and rates of administration differed. Performance was assessed by at least 26 different methods, some of which measured many variables. We examined only results of studies which compared results for a given alcohol concentration (C) measured on the ascending limb (Cup) and the descending limb (Cdown) of the BAC-time curve, whether in paired or parallel-group studies. When subjects were given alcohol in more than one session, we considered results from the first session only. Rating at Cdown was better than at Cup for some measures, as expected if the Mellanby effect were operating. For example, subjects rated themselves less intoxicated on the descending limb than at the same concentration on the ascending limb in 12/13 trials including 229 subjects that gave statistically significant results. In 9 trials with a total of 139 subjects, mean difference could be calculated; weighted for study size, it was 29% [range 24-74%]. Willingness to drive was significantly greater in 4 of 6 studies including a total of 105 subjects; weighted mean difference increased by 207% [range 79-300%]. By contrast, measure of driving ability in three groups of a total of 200 trials in 57 subjects showed worse performance by a weighted mean of 96% [range 3-566%]. In three trials that tested inhibitory control (cued go or no-go response times), weighted mean performance was 30% [range 14-65%] worse on the descending limb. CONCLUSIONS: The "Mellanby effect" has been demonstrated for subjective intoxication and willingness to drive, both of which are more affected at a stated ethanol concentration when BAC is rising than at the same concentration when BAC is falling. By contrast, objective measures of skills necessary for safe driving, such as response to inhibitory cues and skills measured on driving simulators, were generally worse on the descending part of the BAC-time curve for the same BAC.

The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

INTRODUCTION: Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. METHODS: An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. RESULTS: In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. CONCLUSION: The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

Marijuana in the Workplace: Guidance for Occupational Health Professionals and Employers: Joint Guidance Statement of the American Association of Occupational Health Nurses and the American College of Occupational and Environmental Medicine.

Employers are often put in a difficult position trying to accommodate state laws that allow the use of marijuana for medical purposes while enforcing federal rules or company drug-use policies based on federal law. To ensure workplace safety as well as compliance with state and federal legislation, employers should review state laws on discrimination against marijuana users and ensure that policies enacted are consistent with the state's antidiscrimination statutes. Although it appears that in most states that allow medical marijuana use, employers can continue enforcing policies banning or restricting the use of marijuana, this approach may change on the basis of future court decisions. The Joint Task Force recommends that marijuana use be closely monitored for all employees in safety-sensitive positions, whether or not covered by federal drug-testing regulations. Best practice would support employers prohibiting marijuana use at work. Employers, in compliance with applicable state laws, may choose to simply prohibit their employees from working while using or impaired by marijuana. In some states, employers may choose to prohibit marijuana use by all members of their workforce whether on or off duty. Nevertheless, in all cases, a clear policy to guide decisions on when marijuana use is allowed and how to evaluate for impairment must be widely distributed and carefully explained to all workers. Legal consultation during policy development and continual review is imperative to ensure compliance with federal, state, and case law. Drug-use and drug-testing policies should clearly delineate expectations regarding on-the-job impairment and marijuana use outside of work hours. Specific criteria for use by supervisors and HR personnel when referring employees suspected of impairment for an evaluation by a qualified occupational health professional are critical. Detailed actions based on the medical evaluation results must also be clearly delineated for HRs, supervisors, and workers. The Joint Task Force recommends that employers review the following points when developing workplace policies that address marijuana use in the workplace: 1. For employees covered by federal drug testing regulations (eg, DOT and other workers under federal contract), marijuana use, both on or off the job, is prohibited. Thus, employers may use urine drug screening in this population. 2. Employees in safety-sensitive positions must not be impaired at work by any substance, whether it be illicit, legally prescribed, or available over-the-counter. Employers may consider prohibiting on the job marijuana use for all employees in safety-sensitive positions, even when not covered by federal drug testing regulations. Nevertheless, legal review of the employer's policy in the context of state statutes is strongly encouraged. When employers allow medical marijuana use by employees, consultation with a qualified occupational health professional is recommended. 3. Employers residing in or near states that allow the use of recreational marijuana must establish a policy regarding off-work use of marijuana. In many states, the employer may choose to prohibit employees from simply working while using or under the influence of marijuana or may choose to prohibit marijuana use both on and off the job. Urine drug testing above traditional cutoff levels, or serum testing at any level, would be reasonable criteria for the employer wishing to ban both on- and off-the-job use. To detect impairment, a limit of 5 ng/mL of THC measured in serum or plasma as THC (or possibly the sum of THC plus THC-OH for employers who choose to evaluate both psychoactive components) would meet the goal of identifying individuals most likely to be impaired. Nevertheless, employers using the 5 ng/ml level need to understand the limitations of using a single number to fit all cases; therefore, a medical examination focused on identifying impairment is always recommended. Legal consultation is strongly recommended. 4. Although it appears that in most states that allow the use of medical marijuana, employers may be able to continue policies banning or restricting the use of marijuana as previously discussed, this practice may change on the basis of future case law. Currently the ADA does not apply in these situations because marijuana is illegal under federal law. Legal consultation is again strongly recommended. 5. Most workers' compensation statutes allow reduced benefits when a worker is under the influence of alcohol or illegal drugs. Two samples should usually be obtained as a second confirmatory test may be needed. Proof of use and/or impairment is usually required for these cases, and a positive urine drug test (for the inactive metabolite) does not prove acute impairment. The serum level of less than 5 ng/mL could be used for presumptive evidence of impairment in these situations. An MRO is most helpful in helping determine these types of cases because legal testimony may be required. 6. All employers should have clear policies and procedures for supervisors to follow regarding the criteria for identifying potential impairment and the process for referring an employee suspected of impairment for an occupational medical evaluation. Policies should include action required by HR personnel based on the results of the examination. 7. Employee education is vital to ensure compliance with company expectations. Education is needed at hire and again at regular intervals. Workers must know the company's chemical substance policy and management's expectations for adherence. The employer's commitment to a drug-free workplace and existing company policy will influence the education program's content. At a minimum, employees should learn how chemical substances affect their health, safety, personal behavior, and job performance. Supervisors and employees should also be educated about how to recognize behaviors indicative of impairment, whether the source is medical marijuana, prescription medications, illegal drugs, alcohol, over-the-counter medications, fatigue, or any combination thereof. 8. In states where marijuana use is permitted, employers should provide educational resources regarding the detrimental effects of marijuana use, including caution regarding dose and delayed effects of edible products. This information may be obtained from SAMHSA and state governmental agencies. The safety of workers and the public must be central to all workplace policies and employers must clearly articulate that legalization of marijuana for recreational or medical use does not negate workplace policies for safe job performance. The evolving legal situation on medical and recreational marijuana requires employers to consult with legal experts to craft company policy and clarify implications of impaired on-duty workers. This changing environment surrounding marijuana use requires close collaboration between employers, occupational health professionals, and legal experts to ensure that workplace safety is not compromised.

Personal protective equipment and decontamination of adults and children.

Accurate identification of the hazardous material is essential for proper care. Efficient hospital security and triage must prevent contaminated victims from entering the emergency department (ED) and causing secondary contamination. The decontamination area should be located outside the ambulance entrance. Decontamination priorities are protection of the health care worker, utilization of Level C personal protective equipment, and proper decontamination of the exposed patient. Decontamination proceeds in a head-to-toe sequence. Run-off water is a hazardous waste. Hospital and Community Management Planning for these emergencies is essential for proper preparation and effective response to the hazardous materials incident.

Compounded ointment results in severe toxicity in a pediatric patient.

BACKGROUND: Dermal drug delivery is becoming more common, as evidenced by the increased numbers of compounding pharmacies preparing topical products for chronic pain management. Consumers may not appreciate the potency or dangers associated with some of the drugs in these preparations. Pediatric patients are especially at risk for significant toxicity with accidental exposures. We report a case of severe toxicity in an 18-month-old boy from exposure to his father's compounded pain ointment. CASE: An 18-month-old previously healthy child had an ointment applied topically to a diaper rash by his mother, consisting of a single pump of a prescription ointment that her husband received from a compounding pharmacy for neck pain. Approximately 20 minutes later, when the child had been put down for a nap, he had gasping respiration but was otherwise unresponsive. Emergency medical services was called, and the child was unresponsive. In the ED, vital signs were pulse of 57 beats/min, blood pressure 74/35 mm Hg, respiratory rate 21 breaths/min, and O2 saturation 98% on a nonrebreather. Fingerstick glucose was 105 mg/dL. In the ED, physical examination was significant for unresponsiveness, pinpoint pupils, and hyporeflexia. The patient's mental status continued to deteriorate with depressed respirations, and he was intubated. Laboratory results were noncontributory. Electrocardiogram revealed only sinus bradycardia. The patient was transported to a pediatric intensive care unit. He did well over the next several hours with supportive care and had return to normal vital signs over the following 12 hours. He was extubated the following morning without problems. Blood taken at the time of ED presentation had a serum clonidine level of 9.2 ng/mL (reference range, 0.5-4.5 ng/mL) and a norketamine level of 41 ng/mL (reporting limit, >20 ng/mL). CONCLUSIONS: Dermal absorption of drugs leading to significant toxicity in children is well known. Our patient had toxicity from a topical pain medication compounded with several potent drugs known to cause central nervous system depression. There has been an increase in the use of this drug delivery system for management of chronic painful conditions. The popularity and attractiveness of such preparations may be the perception that they are somehow safer and more natural than taking pills. This perception and the fact that these are not dispensed in child-proof containers and are often mailed to the patients without pharmacist counseling can lead to increased inadvertent exposures in the pediatric population.

Postmortem redistribution of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH).

INTRODUCTION: Postmortem redistribution (PMR), a well-described phenomenon in forensic toxicology for certain drugs, can result in increased central blood concentrations relative to peripheral blood concentrations. Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis or marijuana, is the illicit substance most commonly implicated in driving under the influence of drugs (DUID) cases and fatally-injured drivers. No investigation of PMR of THC in human blood has been reported to date. METHODS: Matched heart and iliac postmortem blood specimens were collected from 19 medical examiner cases (16 Males, 3 Females) with positive cannabinoid urine immunoassay screens. THC, its equipotent metabolite 11-hydroxy-THC (11-OH-THC) and non-psychoactive metabolite 11-nor-9-carboxy-THC (THCCOOH) were quantified by two-dimensional gas chromatography-mass spectrometry with cryofocusing, with 0.5 ng/mL limits of quantification (LOQ) for all analytes. RESULTS: 10 cases had quantifiable THC and 11-OH-THC; THCCOOH was present in all 19. Median (range) heart:iliac blood ratios were 1.5 for THC (range: 0.3-3.1); 1.6 for 11-OH-THC (range: 0.3-2.7); and 1.8 for THCCOOH (range: 0.5-3.0). DISCUSSION: Cannabinoids, in general, exhibited a mean and median central:peripheral (C:P) concentration ratio of less than 2 following death. A trend was observed for greater PMR with increasing postmortem interval between death and sampling. To our knowledge, these are the first data on THC PMR in humans, providing important scientific data to aid in the interpretation of postmortem cannabinoid concentrations in medico-legal investigations.

Osmol gap method for the detection of diethylene glycol in human serum.

BACKGROUND: Measurement of the osmol gap (OG) is a technique that is used frequently in toxic alcohol poisonings (ethylene glycol (EG) and methanol) as a rapid means to estimate exposure, and can be performed in virtually all hospital laboratories. The value of the OG has not been previously evaluated for diethylene glycol (DEG) exposures. The primary objective of this study was to evaluate the utility of the OG in estimating DEG serum concentrations using the most common formula that is currently used for estimating methanol, ethanol, and ethylene glycol concentrations. METHODS: This was a controlled laboratory investigation using serum samples individually spiked with a known quantity of toxic alcohol compared to no toxic alcohol. Test samples were spiked with ethanol, DEG, EG, and methanol. Serum chemistries and osmolality and osmolarity were determined, and the OG was determined for each specimen. RESULTS: The percent error of estimating DEG concentrations of 26.3% was similar to the mean percent error for estimating other alcohol concentrations, 30.5%±5.6% (P>0.05, 95% confidence interval 16.7%-44.3%). CONCLUSIONS: The severity of metabolic effects associated with DEG and the need to appropriately determine rescue treatments mandate early detection of significant exposures for effective triage and patient management. Our results indicate that the percent error of the osmol gap method for estimating DEG concentration is similar to that of other toxic alcohols; this simple technique could be a valuable clinical tool, since quantitative DEG analysis is rarely available.

Diethylene glycol: widely used solvent presents serious poisoning potential.

OBJECTIVE: To describe the serious toxicity of a readily available solvent, diethylene glycol (DEG). We describe a case of intentional ingestion of a wallpaper stripper containing DEG resulting in severe multi-system organ failure. CASE REPORT: A 27-year-old male presented to the Emergency Department (ED) one day after ingesting wallpaper stripper containing DEG. He developed acidosis, renal cortical necrosis, hepatocellular injury, and severe neurologic sequelae, including cranial neuropathies and peripheral demyelinating sensori-motor polyneuropathy. His neurologic function improved over 5 months. DISCUSSION: Our case demonstrates the severe toxicity of DEG. DEG is present in numerous formulations, often without proper protective packaging. DEG has been associated with severe epidemic poisonings in the past and with the availability of safer alternatives, DEG in consumer products should be eliminated. CONCLUSION: DEG is found in numerous products. Delays in treatment can have devastating results, resulting in death or permanent disability. The pervasive use of this compound makes further human exposures likely.

Profound metabolic acidosis and oxoprolinuria in an adult.

INTRODUCTION: Profound metabolic acidosis in critically ill adults sometimes remains unexplained despite extensive evaluation. CASE REPORT: A 58-year-old female presented in a confused state to the emergency department; she had been confused for several days. Laboratory evaluation revealed a high anion gap metabolic acidosis and modestly elevated acetaminophen level. Lactic acid was only modestly elevated. There was no evidence of ketoacids, salicylate, methanol, or ethylene glycol. A urine sample submitted on day 1 of hospitalization revealed a markedly elevated level of 5-oxoproline. DISCUSSION: Originally described in children with an inherited defect of glutathione synthetase, 5-oxoproline is an unusual cause of metabolic acidosis. More recently this disturbance has been recognized in critically ill adults without a recognized inherited metabolic disorder. In most of these cases there has been the concomitant use of acetaminophen. Any causal relationship between acetaminophen and this disturbance is speculative. CONCLUSION: In critically ill adults with unexplained metabolic acidosis, 5-Oxoproline should be considered in the differential.